Medical Devices

ABSTRACT

The invention relates to medical balloons, and methods of modifying said balloons by forming a void pattern in their exterior surfaces and filling the voids with a material, such as a fiber or a nanomaterial (e.g., nanotubes, such as carbon nanotubes) and a matrix material, e.g., a polymer.

RELATED APPLICATIONS

This application is a continuation of co-pending U.S. application Ser.No. 11/060,093, filed Feb. 17, 2005, entire disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

The invention relates to medical devices, such as, for example, medicalballoons, and related methods.

BACKGROUND

The body includes various passageways such as arteries, other bloodvessels, and other body lumens. These passageways, such as a coronaryartery, sometimes become constricted or blocked, for example, by plaqueor by a tumor. When this occurs, the constricted passageway can bewidened in an angioplasty procedure using a balloon catheter, whichincludes a medical balloon carried by a catheter shaft.

In an angioplasty procedure, the balloon catheter can be used to treat astenosis, or a narrowing of the body vessel, by collapsing the balloonand delivering it to a region of the vessel that has been narrowed tosuch a degree that fluid (e.g., blood) flow is restricted. The ballooncan be delivered to a target site by passing the catheter shaft over anemplaced guidewire and advancing the catheter to the site. In somecases, the path to the site can be rather tortuous and/or narrow. Uponreaching the site, the balloon is then expanded, for example, byinjecting a fluid into the interior of the balloon. Expanding theballoon can expand the stenosis radially so that the vessel can permitan acceptable rate of fluid flow. After use, the balloon is collapsed,and the catheter is withdrawn.

SUMMARY

The invention relates to medical devices, such as medical balloons, andrelated methods. In some aspects, a medical balloon wall can have a voidin its exterior surface. The void can be formed, for example, byablation (e.g., laser ablation), and/or can be in the form of a groove.In embodiments, the void can form a void pattern in the balloon wall.The void can be filled with a material, such as a fiber or ananomaterial (e.g., nanotubes, such as carbon nanotubes). In someembodiments, the void can be filled with a composite that includes ananomaterial and, e.g., a polymer. In embodiments, the balloon exhibitsenhanced burst pressure, profile and/or flexibility. In certainembodiments, the burst pressure of the balloon can be at least about 10atm.

Embodiments may include one or more of the following advantages.

A balloon is provided that exhibits favorable burst pressure andflexibility characteristics. The addition of a nanomaterial into a voidand/or an ablated region of a balloon can enhance the burst pressure ofthe balloon while maintaining the profile and/or flexibility of theballoon. In embodiments, a balloon that includes a nanomaterial in avoid and/or an ablated region can have a relatively high burst pressure,good flexibility, and a relatively low profile. The nanomaterial can berelatively biocompatible. In some embodiments, the nanomaterial candeliver a therapeutic agent, drug, and/or pharmaceutically activecompound to a target site within the body. A void or an ablated regioncan be formed in a balloon wall relatively quickly and easily. The voidor ablated region can be formed to a relatively high degree of precision(e.g., in embodiments in which the void or ablated region is formed bylaser ablation).

Still further aspects, features, and advantages follow.

DESCRIPTION OF DRAWINGS

FIG. 1 is a cross-sectional side view of an embodiment of a ballooncatheter;

FIG. 2A is a side view of an embodiment of a medical balloon;

FIG. 2B is a cross-sectional side view of the medical balloon of FIG.2A;

FIG. 2C is an enlarged view of region 2C in FIG. 2B;

FIGS. 3A and 3B illustrate a process for forming the medical balloon ofFIGS. 2A and 2B;

FIG. 4 is a cross-sectional side view of an embodiment of a medicalballoon;

FIG. 5 is a cross-sectional side view of a region of an embodiment of amedical balloon;

FIG. 6 is a cross-sectional side view of a region of an embodiment of amedical balloon; and

FIG. 7 is a cross-sectional side view of a region of an embodiment of amedical balloon.

DETAILED DESCRIPTION

Referring to FIG. 1, a rapid-exchange balloon catheter 100 includes acatheter shaft 105 having a proximal end 110 and a distal end 120, and aballoon 200 carried by the catheter shaft at the distal end. Cathetershaft 105 includes a proximal outer portion 150, a distal outer portion170 connected to the proximal outer portion, and a distal inner portion180 connected to the distal outer portion. At proximal end 110, ballooncatheter 100 includes a manifold 130 connected to proximal outer portion150 by a sheath 140 for a hypotube 160.

Balloon catheter 100 can be used as follows. An operator of ballooncatheter 100 delivers distal end 120 of balloon catheter 100 into a bodylumen (e.g., a blood vessel) over an emplaced guidewire. Manifold 130can be used to control the positioning of distal end 120 of ballooncatheter 100 in the body lumen. Balloon catheter 100 is navigatedthrough the body lumen to position balloon 200 at a treatment site. Onceballoon 200 reaches the treatment site, balloon 200 is inflated withinflation fluid, so that balloon 200 contacts the wall of the bodylumen. Manifold 130 can be used to control the delivery of the inflationfluid to balloon 200. After balloon 200 has been inflated to contact thewall of the body lumen, balloon 200 is deflated and removed from thebody lumen by withdrawing it, typically into an introducer sheath.Alternatively or additionally, balloon 200 can be used to deliver amedical device (e.g., a stent, a graft) and/or to block a passageway.Balloons and balloon catheters are described, for example, in Solar,U.S. Pat. No. 4,976,590,and Wang, U.S. Pat. No. 5,195,969. Stents aredescribed, for example, in Heath, U.S. Pat. No. 5,725,570. The stent caninclude a coating, such as a drug elution layer.

Referring now to FIGS. 2A-2C, balloon 200 has a wall 210 with a patternof grooves 220 formed in the balloon wall. A reinforcing material,particularly a nanomaterial 230, is disposed within grooves 220. Theballoon exhibits favorable burst pressure and flexibilitycharacteristics by combination of the balloon wall material, reinforcingmaterial, and groove pattern. In embodiments, the balloon wall materialis relatively soft and flexible; flexibility can be further enhanced bythe groove pattern, which facilitates refolding and reduced withdrawalforce. The reinforcing material is selected to enhance the burstpressure of the grooved balloon while maintaining improved flexibility.In other embodiments, the balloon wall includes a relativelynondistendible high burst material, such as a biaxially orientedpolymer. The groove pattern can enhance flexibility of the balloon. Thereinforcing material can maintain burst pressure and enhancedflexibility. In some embodiments, the burst pressure of the balloon iswithin about ±50% of the burst pressure of a similar balloon without agroove pattern and reinforcing material. In certain embodiments, theburst pressure of the balloon is within about ±20% (e.g., about ±10% or±5%), of the burst pressure of a similar balloon without a groovepattern and reinforcing material.

Referring particularly to FIGS. 2A and FIG. 2C, the groove ischaracterized by its pattern and dimensions. Referring particularly toFIG. 2A, a pattern of intersecting circumferential groove sections isillustrated which define a regular pattern of non-grooved land areas225. This permits a reinforcing material to be supplied to the groovesin a pattern similar to a braid, which enhances flexibility alongmultiple axes relative to the balloon axis, and which can assistrefolding during balloon deflation and can facilitate deflection orrefolding when the deflated balloon encounters the body lumen orintroducer sheath during withdrawal. The density of the pattern definesrelatively small land areas 225 between the groove sections, whichenhances the reinforcing function of the reinforcing material, therebyincreasing burst pressure. In embodiments, groove sections can benon-intersecting, e.g., a continuous spiral or a double helix. Groovesections can be continuous or intermittent. The pattern can beasymmetric. Such asymmetric patterns may, for example, encouragedeflation or refolding in a particular direction.

Wall 210 has a thickness “T_(W)” and groove 220 has a depth “D_(G)” anda width “W_(G)”. Balloon flexibility is enhanced by increased groovedepth and width. The specificity of deflection along a particular axisis enhanced by a narrower groove width. In embodiments, the ratio ofgroove width to depth is about 10 to 1 or less, e.g. about 1 to 1 orless. In embodiments, the groove depth can be at least about 1% of theballoon wall thickness, and/or about 95% or less of the balloon wallthickness (e.g., about 75% or less, about 25% or less, from about 5% toabout 75%). In embodiments, the cross-sectional profile of the grooveexhibits substantially vertical walls extending from a substantiallyplanar floor, as illustrated. Alternatively, the profile is v-shaped orcurved, e.g., hemispherical. The profile can be varied along the lengthof a groove.

In some embodiments, thickness “T_(W)” of wall 210 can be up to about0.02 inch (e.g., from about 0.0003 inch to about 0.013 inch).Alternatively or additionally, depth “D_(G)” of groove 220 can be up toabout 50 microns (e.g., from about 0.5 micron to about 25 microns). Incertain embodiments, width “W_(G)” of groove 220 can be up to about 1500microns (e.g., from about one micron to about 1000 microns). Inembodiments, at least one of the dimensions of groove 220 (e.g., depth“D_(G)”, width “W_(G)”) can be nano-sized (less than about 1000 nm). Forexample, depth “D_(G)” and/or width “W_(G)” can be less than about 750nm (e.g., less than about 500 nm).

The reinforcing material is selected for its reinforcingcharacteristics, e.g., its ability to enhance burst pressure in thepattern defined by the grooves, and its flexibility. Particularly, thereinforcing material includes nanomaterials. Nanomaterial 230 includesparticles and/or fibers having at least one dimension less than about1000 nm. In some embodiments, nanomaterial 230 can include nanotubes.The nanotubes can be, for example, single-walled nanotubes (SWNT) ormulti-walled nanotubes (MWNT). In some embodiments, the nanotubes can bedouble-walled nanotubes (DWNT). Examples of nanotubes include carbonnanotubes, such as hollow carbon nanotubes (e.g., hollow single walledcarbon nanotubes, hollow multiwalled carbon nanotubes (sometimes calledbuckytubes)); ceramic nanotubes, such as boron nitride nanotubes andaluminum nitride nanotubes; and metallic nanotubes, such as goldnanotubes. Carbon nanotubes are available from, for example, RiceUniversity. Synthesis of carbon nanotubes is described, for example, inBronikowski et al., J. Vac. Sci. Technol. A, 19(4), 1800-1805 (2001);and Davis et al., Macromolecules 2004, 37, 154-160. Boron nitridenanotubes are available from the Australian National University(Canberra, Australia). In certain embodiments, nanomaterial 230 caninclude more than one type of nanotube. Nanomaterial 230 can bepositively or negatively charged, or can be neutral. Nanomaterial 230can include one or more metals or metal alloys, such as stainless steel.In some embodiments, nanomaterial 230 can include one or more polymers,such as high-density polyethylene (HDPE). In certain embodiments,nanomaterial 230 can include a nanoclay, such as montmorillonite clay.Nanomaterials are described, for example, in commonly assigned U.S. Ser.No. 10/850,087, filed on May 20, 2004, and entitled “Medical Devices”,which is incorporated herein by reference in its entirety.

In some embodiments, nanomaterial 230 can be bonded to balloon 200 byone or more other materials. For example, nanomaterial 230 can be bondedto balloon 200 by an adhesive, such as a UV-curable acrylate resin. Incertain embodiments, nanomaterial 230 can be dispersed in a polymer toform a polymer composite that is then bonded to balloon 200. Examples ofsuitable polymers are provided infra with reference to the balloon wallmaterial. In embodiments in which nanomaterial 230 is dispersed in apolymer to form a polymer composite, the polymer composite can furtherinclude one or more additives that enhance formation of the composite.For example, the polymer composite can include one or more coupling orcompatibilizing agents, dispersants, stabilizers, plasticizers,surfactants, and/or pigments that enhance interactions between thenanomaterial and the polymer(s). Examples of additive(s) are describedin U.S. Patent Application Publication No. US 2003/0093107, published onMay 15, 2003, which is incorporated herein by reference.

In some embodiments, nanomaterial 230 can be modified to enhanceinteractions between the components of the nanomaterial and/or betweenthe nanomaterial and other materials. As an example, in embodiments inwhich nanomaterial 230 includes nanotubes, the nanotubes can be modifiedto enhance interactions between the nanotubes and a polymer in wall 210of balloon 200. As another example, the nanotubes can be modified toenhance interactions between the nanotubes and a polymer within whichthe nanotubes are dispersed. For example, the nanotubes can bechemically modified with one or more functional groups that increaseinteractions (e.g., compatibility) between the nanotubes and thepolymer. Functionalization of carbon nanotubes is described, forexample, in Bahr et al., J. Am. Chem. Soc. 2001, 123, 6536-6542, and inU.S. Patent Application Publication No. US 2003/0093107, published onMay 15, 2003, both of which are incorporated herein by reference.Alternatively or additionally, nanotubes can be connected orcrosslinked, for example, by irradiation. Irradiation of carbonnanotubes is described, for example, in Krasheninnikov et al., Phys.Rev. B 66, 245403 (2002); and in commonly assigned U.S. Ser. No.10/850,085, filed on May 20, 2004, and entitled “Medical Devices andMethods of Making the Same”, both of which are incorporated herein byreference in their entirety.

In particular embodiments, the reinforcing material fills the grooves.As shown in FIGS. 2B and 2C, nanomaterial 230 fills grooves 220, suchthat the profile of balloon 200 is generally smooth. In otherembodiments, the nanomaterial does not fill the groove or overfills thegroove to provide a morphology on the balloon surface. A morphology onthe exterior surface can, e.g., aid stent retention during delivery.

Balloon 200 (e.g., wall 210 of balloon 200) can include, for example,one or more polymers (e.g., a mixture of polymers). For example, balloon200 can include one or more thermoplastics and/or thermosets. Examplesof thermoplastics include polyolefins; polyamides (e.g., nylon, such asnylon 12, nylon 11, nylon 6/12, nylon 6, nylon 66); polyesters (e.g.,polyethylene terephthalate (PET), polybutylene terephthalate (PBT),polyethylene naphthalate (PEN), polytrimethylene terephthalate (PTT));polyethers; polyurethanes; polyvinyls; polyacrylics; fluoropolymers;copolymers and block copolymers thereof, such as block copolymers ofpolyether and polyamide (e.g., PEBAX®); and mixtures thereof. Examplesof thermosets include elastomers (e.g., EPDM), epichlorohydrin,polyureas, nitrile butadiene elastomers, and silicones. Other examplesof thermosets include epoxies and isocyanates. Biocompatible thermosetsmay also be used. Biocompatible thermosets include, for example,biodegradable polycaprolactone, poly(dimethylsiloxane) containingpolyurethanes and ureas, and polysiloxanes. Ultraviolet curablepolymers, such as polyimides, can also be used. Other examples ofpolymers that can be used in balloon 200 include polyethylenes,polyethylene ionomers, polyethylene copolymers, polyetheretherketone(PEEK), thermoplastic polyester elastomers (e.g., HYTREL®), andcombinations thereof. The balloon can include multiple layers provided,e.g., by coextrusion. Other polymers are described, for example, incommonly assigned U.S. Ser. No. 10/645,055, filed on Aug. 21, 2003, andentitled “Medical Balloons”, which is incorporated herein by reference.

In embodiments, balloon 200 can have a burst pressure of at least about5 to 10 atm (e.g., about 10 atm or greater). In certain embodiments,balloon 200 can have a burst pressure of up to about 30 atm or up toabout 40 atm. As referred to herein, the burst pressure of a balloonrefers to the internal pressure at which the balloon bursts. One way theburst pressure of a balloon is determined is by measuring the internalpressure of the balloon as the balloon is inflated at a rate of two psiper second with a 10 second hold at every 50 psi interval until theballoon bursts.

In particular embodiments, the balloon includes a semi-distendible(semi-compliant) polymer, and has a groove pattern with a nanomaterialreinforcing material.

Compared to a similar balloon without grooves or nanomaterial, theballoon exhibits increased burst pressure and a comparable flexibility.In particular embodiments, the balloon includes a substantiallynondistendible (non-compliant) polymer, and has a groove pattern withnanomaterial. Compared to a similar balloon without grooves ornanomaterial, the balloon exhibits comparable or improved burst pressureand improved flexibility. In particular embodiments, the balloon issized for use in the vascular system, e.g., the coronary arteries. Inother embodiments, the balloon is configured for use in other bodylumens such as the GI tract. In some embodiments, the balloon can beconfigured for use in urological (e.g., urinary) applications.

In some embodiments, a balloon parison can be formed and then stretchedand inflated to form a balloon precursor, and grooves 220 can thereafterbe ablated into the wall of the balloon precursor. In certainembodiments, a balloon parison can be formed, and grooves 220 can beablated into the surface of the parison. Then, the balloon parison canbe stretched and expanded to form a balloon precursor. After the balloonprecursor has been formed, the grooves 220 can be filled withnanomaterial 230.

A balloon can be formed using any suitable technique, such as blowmolding, film molding, injection molding, and/or extrusion. For example,a polymer tube can be extruded, and can thereafter be stretched andblown to form a balloon. Methods of making medical tubing are described,for example, in commonly assigned U.S. Patent Application PublicationNo. US 2004/0078052 A1, published on Apr. 22, 2004, which isincorporated herein by reference. Methods of forming a balloon from atube are described, for example, in commonly-assigned U.S. Ser. No.10/263,225, filed Oct. 2, 2002, and entitled “Medical Balloon”;Anderson, U.S. Pat. No. 6,120,364; Wang, U.S. Pat. No. 5,714,110; andNoddin, U.S. Pat. No. 4,963,313, all incorporated herein by reference intheir entirety. After it has been formed, balloon 200 can be attached tocatheter shaft 105 by, for example, laser bonding. Other attachmentmethods are described, for example, in references incorporated herein.Catheter shaft 105 may also be any of the multilayer tubes described incommonly assigned U.S. Ser. No. 10/645,014, filed Aug. 21, 2003, whichis incorporated herein by reference.

Grooves 220 can be formed, for example, by laser ablation. Laserablation of balloons is described, for example, in commonly assignedU.S. patent application Ser. No. 11/060,151, filed Feb. 17, 2005, whichis incorporated herein by reference.

FIGS. 3A and 3B illustrate a method for filling grooves 220 withnanomaterial 230. In FIGS. 3A and 3B, a balloon precursor 300, whichincludes grooves 220, is moved (in the direction of arrow “A”) toward avat 310 that includes a solvent 320 and a nanomaterial 230 dispersedwithin the solvent. Solvent 320 can be, for example, water or a polymer(e.g., a polysaccharide, a polyvinyl alcohol). As FIG. 3B shows, onceballoon precursor 300 is partially submerged in solvent 320, balloonprecursor 300 is rotated in solvent 320 (in the direction of arrows A1and A2), so that nanomaterial 230 attaches to balloon precursor 300.Solvent 320 facilitates the application of nanomaterial 230 to balloonprecursor 300. After balloon precursor 300 has been fully rotated insolvent 320, balloon precursor 300 is removed from solvent 320.Thereafter, excess nanomaterial (nanomaterial that is not within grooves220) is removed from balloon precursor 300 by, for example, one or morewipers that wipe off the surface of balloon precursor 300. Alternativelyor additionally, excess nanomaterial can be removed from balloonprecursor 300 by pulling balloon precursor 300 through a die. At the endof the process, balloon 200 has been formed.

In some embodiments, the outer surface of balloon precursor 300 iscovered by a removable layer, such as a wax layer. Grooves 220 are thenformed through the removable layer into the balloon wall. While grooves220 are not covered by the wax layer, the land areas 330 that are formedbetween the grooves are covered by the wax layer. Balloon precursor 300is then dipped into solvent 320, such that nanomaterial 230 fillsgrooves 220 and covers land areas 330. Thereafter, balloon precursor 300is removed from solvent 320, and the wax is removed (e.g., by peelingthe wax off of land areas 330 or by solvating the wax) to produceballoon 200.

Alternatively or additionally, in embodiments in which nanomaterial 230is charged, balloon precursor 300 can be charged (e.g., via plasmatreatment). Thereafter, a charged polyelectrolyte (e.g.,poly(ethyleneimine)) can be layered onto balloon precursor 300 (e.g.,into grooves 220). Balloon precursor 300 can then be exposed to, forexample, charged nanotubes (e.g., in a solvent) that can attach to thecharged sections of balloon precursor 300. In some embodiments, anotherpolyelectrolyte layer can be added to balloon precursor 300, and can befollowed by the addition of another nanotube layer. This layering cancontinue as desired. After a suitable amount of nanomaterial 230 hasbeen added to balloon precursor 300, a curing agent (e.g.,glutaraldehyde) can be used to cure the nanomaterial and polyelectrolytelayer(s). Polyelectrolyte layering processes are described, for example,in U.S. patent application Ser. No. 10/849,742, filed on May 20, 2004,and entitled “Medical Devices Having Multiple Layers”, and in NatureMaterials, Vol. 1 (November 2002), 190-194, both of which areincorporated herein by reference.

In embodiments, nanomaterial 230 can be added to grooves 220 of balloonprecursor 300 via hydrophilic and/or hydrophobic interactions betweenthe nanomaterial and the grooves. For example, both the nanomaterial andthe grooves can be hydrophilic, while land areas 330 of balloonprecursor 300 are hydrophobic, such that the nanomaterial may beattracted to the grooves and repelled by the land areas. As a result,the nanomaterial may fill the grooves without also coating the landareas. In some embodiments, both the nanomaterial and the grooves can behydrophobic, while the land areas are hydrophilic, such that thenanomaterial may fill the grooves without also coating the land areas.

In certain embodiments, balloon precursor 300 can be functionalized(e.g., via a chemical reaction) as the balloon precursor is beingablated. For example, a reactive gas (e.g., plasma gas) can beintroduced into grooves 220 as the grooves are being formed by ablation.The reactive gas can, e.g., cause the grooves to become charged, and tothereby attract a charged nanomaterial.

Nanomaterial 230 may be inherently hydrophilic or hydrophobic, or can berendered hydrophilic or hydrophobic by, for example, chemicalmodification, such as the addition of one or more functional groups tothe nanomaterial (described supra). Alternatively or additionally, thenanomaterial may be dispersed in a hydrophilic or hydrophobic solventthat can then be used to deliver the nanomaterial to the correspondinghydrophilic or hydrophobic groove(s) in the balloon precursor. Inembodiments, grooves 220 and/or land areas 330 of balloon precursor 300can be formed of, for example, a polymer. The polymer may be inherentlyhydrophilic or hydrophobic, or may be rendered hydrophilic orhydrophobic via the addition of one or more functional groups. Examplesof hydrophilic functional groups include hydroxyl groups, carbonylgroups, carboxyl groups, and carboxylate groups. Examples of hydrophobicfunctional groups include hydrocarbons, silicones, and fluorocarbons. Incertain embodiments, the land areas and/or grooves of the balloonprecursor may be selectively coated with a hydrophilic or hydrophobiccoating (e.g., a hydrophilic polymer coating, such as poly(hydroxyethylmethacrylate) or polyethylene oxide). For example, the land areas can becovered with a protective layer (e.g., a wax layer) such that thegrooves can be coated without also coating the land areas. After thegrooves have been coated, the protective layer can be removed from theland areas. Methods for making polymers and/or nanomaterials hydrophilicor hydrophobic are described, for example, in Richard J. LaPorte,Hydrophilic Polymer Coatings for Medical Devices (Technomic PublishingCo., Inc., 1997), and in Velasco-Santos et al., “Improvement of Thermaland Mechanical Properties of Carbon Nanotube Composites Through ChemicalFunctionalization”, Chem. Mater. 15 (2003), 4470-4475, both of which areincorporated herein by reference.

Other methods of attaching nanomaterial 230 to balloon precursor 300include spraying. In some embodiments, a mixture containing nanotubesand a solvent (e.g., 1,1,2,2-tetrachloroethane) can be sprayed ontoballoon precursor 300 to form balloon 200. The solvent can evaporate,resulting in a layer of nanotubes, sometimes called bucky paper, on thesurface of the balloon (e.g., in grooves 220).

While methods of adding a nanomaterial into the grooves of a balloonprecursor without also adding the nanomaterial into the land areas ofthe balloon precursor have been described, in certain embodiments, ananomaterial can be added into both the grooves and the land areas of aballoon precursor. For example, a balloon precursor with grooves andland areas can be sprayed with a nanomaterial solution, such that thenanomaterial solution both fills the grooves and coats the land areas.As an example, FIG. 4 shows a balloon 700 that has a wall 702 with apattern of grooves 704 formed in the balloon wall. Wall 702 has aninterior surface 706 and an exterior surface 708. Nanomaterial 710covers exterior surface 708 of wall 702, and fills grooves 704. Whilenot shown, in some embodiments, the thickness of a nanomaterial layer ona balloon surface can vary in different regions of the balloon surface.For example, one region of a balloon surface can have a thicker layer ofnanomaterial disposed on it than another region of the balloon surface.

While certain embodiments have been described, other embodiments arepossible.

As an example, while a single-layer balloon has been shown, in someembodiments, a balloon that includes an ablated region can be amultilayer balloon. For example, the balloon can have two, three, four,five, or six layers. A multilayer balloon can be formed by, for example,coextrusion. In certain embodiments in which the balloon is a multilayerballoon (e.g., a balloon having five layers), the ablated region mayextend into only the top layer or the top two layers of the balloon.

As an additional example, in some embodiments, a balloon can includemore than one type and/or size of nanomaterial. For example, a groove inthe balloon can include both carbon nanotubes and ceramic nanotubes. Incertain embodiments, the balloon can be formed of a polymer compositeincluding one type of nanomaterial, and a groove in the balloon wall canbe filled with another type of nanomaterial.

As a further example, in certain embodiments, a nanomaterial (such asnanotubes) that is combined with chitosan, chondroitin, and/or DNA canbe added to a balloon or balloon precursor.

In certain embodiments, and referring now to FIGS. 5-7, a groove in aballoon wall can be filled with a nanomaterial and then covered with aprotective layer. For example, FIG. 5 shows a balloon wall 400 with agroove 410, and nanomaterial 420 filling the groove. A protective layer430 covers groove 410, and is flush with surface 440 of balloon wall400. As another example, FIG. 6 shows a balloon wall 500 with a groove510 that is filled with nanomaterial 520. A protective layer 530 coversboth groove 510 and surface 540 of balloon wall 500. In someembodiments, a balloon can include a protective layer that fills aportion or all of a groove in a wall of the balloon. For example, FIG. 7shows a balloon wall 800 with a groove 810, and a nanomaterial 820filling the groove. A protective layer 830 covers both groove 810 andsurface 840 of balloon wall 800, while also filling groove 810.Protective layers 430, 530, and 830 can be formed, for example, from oneor more polymers, such as elastomers, modified UV-curable polyesteracrylate resins (e.g., acrylate/acetoacetate synthesized by a Michaelreaction), polyurethanes, and/or polyethers. In some embodiments, aprotective layer can be formed of a UV-curable (e.g., UV-crosslinkable)polymer (e.g., a polyester) that, when cured by ultraviolet radiation,can enhance bonding of the nanomaterial to the grooves of the balloon.While not shown, in some embodiments, a protective layer such aspolyurethane can cover substantially all of the outer surface of aballoon. Other examples of materials that can be used in a protectivelayer include polymers such as PEBAX®, HYTREL®, andpolyisobutylene-polystyrene block copolymers (e.g.,styrene-isobutylene-styrene). Polymers are described, for example, inPinchuk et al., U.S. Pat. No. 6,545,097, which is incorporated herein byreference. In some embodiments in which the balloon includes aprotective layer, the material filling the grooves in the balloon maynot be biocompatible. In such embodiments, the protective layer canprotect the body from exposure to the non-biocompatible material. Incertain embodiments in which the balloon includes a protective layer,the material filling the grooves may be water-soluble. In suchembodiments, the protective layer can prevent the water-soluble materialfrom dissolving upon contact with, for example, blood.

As another example, in some embodiments, a nanomaterial can be added toa balloon by dissolving the nanomaterial in a solvent to form asolution, and then applying the solution to the balloon. The solutioncan be applied to the balloon by, for example, injection through asyringe. In certain embodiments, some of the water can be removed fromthe solution (e.g., by evaporation) to form a gel, and the gel can beapplied to the balloon. A carbon nanotube solution can be formed, forexample, by dissolving carbon nanotubes in water using arabic gum.Suitable carbon nanotube-arabic gum solutions are described, forexample, in R. Bandyopadhyaya et al., “Stabilization of IndividualCarbon Nanotubes in Aqueous Solutions”, Nano Letters, 2 (2002), 25-28,which is incorporated herein by reference. In some embodiments, a carbonnanotube solution can be formed by dissolving carbon nanotubes in waterusing polymer-wrapping techniques, such as those described in Michael J.O'Connell et al., “Reversible Water-Solubilization of Single-WalledCarbon Nanotubes by Polymer Wrapping”, Chem. Phys. Letters 342 (2001),265-271, which is incorporated herein by reference. In certainembodiments, a nanotube solution can be made by adding nanotubes (e.g.,single-walled nanotubes (SWNT)) into a surfactant (e.g., 1% by weightaqueous sodium dodecyl sulfate (SDS)), homogenizing the resultingmixture for about one hour (e.g., at about 6500 revolutions per minute),and then sonicating the mixture (e.g., for about 10 minutes). Theresulting solution can be applied to a balloon by, for example, sprayingthe solution onto the balloon (e.g., using an ultrasonic nozzle, such asa MicroMist system from Sono-Tek). In some embodiments, methanol canalso be sprayed onto the balloon to help remove the surfactant from thenanotubes and thereby drive the nanotubes out of solution and onto theballoon surface. The formation and casting of nanotube solutions isdescribed, for example, in A. Meitl et al., “Solution Casting andTransfer Printing Single Walled Carbon Nanotube Films”, Nano Letters 4:9(2004), 1643-1747, which is incorporated herein by reference.

As an additional example, in some embodiments, nanomaterial (e.g.,nanotubes) can be applied to a balloon or balloon precursor using apicoliter dispenser, such as a picoliter dispenser from Microdrop GmbH(Germany). In certain embodiments, a solution including nanomaterial canbe added onto a balloon or balloon precursor using a picoliterdispenser.

As a further example, in certain embodiments, a balloon that includesone or more ablated regions can include a fiber that is wound throughthe ablated region(s). In some embodiments, the fiber can includenanomaterial (e.g., nanotubes) within it (e.g., for reinforcement). Thefiber can allow high loading (e.g., up to about 50% by weight) ofnanomaterial on the balloon. Nanotube-containing fibers can be formed,for example, by electrospinning, described in Ko et al., Adv. Mater.2000, 15, No. 14, July 17, 1161-1163; and “Carbon Nanotube ReinforcedCarbon Nano Composite Fibrils By Electro-Spinning”, thesis by Ashraf AbdEl-Fattah Ali, Drexel University, October 2002. In certain embodiments,the fiber may not contain any nanomaterial in it. The fiber can be, forexample, a long, continuous fiber that is not nano-sized and that doesnot include any nanomaterial in it. In such embodiments, the balloon mayor may not contain nanomaterials (e.g., in the same groove in which thefiber is wound). In some embodiments, a fiber can include one or morepolymers, such as ultra-high molecular weight polyethylene, polyesters,and polymeric aromatic amides (e.g., Kevlar®, available from DuPont). Incertain embodiments, a fiber can include spider silk; in some suchembodiments, the fiber can be substantially formed of spider silk.

In certain embodiments, one or more fibers can be added to a balloon ora balloon precursor by electrospinning. For example, a carbon fiber canbe electrospun onto the surface (e.g., into a groove) of a balloon. Insome embodiments, a fiber can be electrospun into one or more grooves ina balloon, and the balloon can thereafter be disposed within a mold.Heat and/or internal pressure can then be applied to the balloon, tohelp attach or integrate the fiber into the groove. Electrospinning isdescribed, for example, in Zheng-Ming Huang et al., “A Review on PolymerNanofibers by Electrospinning and Their Applications in Nanocomposites”,Composites Science and Technology 63 (2003), 2223-2253, and in Sian F.Fennessey et al. and Richard J. Farris, “Fabrication of Aligned andMolecularly Oriented Electrospun Polyacrylonitrile Nanofibers and theMechanical Behavior of Their Twisted Yarns”, Polymer 45 (2004),4217-4225, both of which are incorporated herein by reference. Incertain embodiments, one or more therapeutic agents and/orpharmaceutically active compounds (such as those described below) can beincorporated (e.g., embedded) into one or more fibers that areelectrospun onto a balloon or balloon precursor. In certain embodiments,one or more fibers can be electrospun onto a balloon and/or balloonprecursor from a solution that includes one or more therapeutic agentsand/or pharmaceutically active compounds. As a result, the fibers thatare electrospun onto the balloon and/or balloon precursor can includethe therapeutic agent(s) and/or pharmaceutically active compound(s). Insome embodiments, the electrospun fibers can be porous, and/or can bemade out of a biodegradable material, such that the electrospun fiberscan release a therapeutic agent and/or pharmaceutically active compoundduring use (e.g., through the pores in the fibers and/or as thebiodegradable material biodegrades).

As another example, in some embodiments, a balloon can include one ormore nanocomposites. For example, a balloon can include one or moregrooves that are filled with a nanocomposite. Nanocomposites aredescribed, for example, in Parsonage et al., U.S. Patent ApplicationPublication No. US 2003/0093107 A1, published on May 15, 2003, which isincorporated herein by reference.

As an additional example, in certain embodiments, a balloon can includeone or more grooves that are randomly located on the balloon surface(i.e., that do not form a pattern on the balloon surface). In certainembodiments, one or more of the grooves can be filled with, for example,a nanomaterial and/or a fiber. Alternatively or additionally, a ballooncan include grooves that have different thicknesses and/or widths.

In some embodiments, one or more of the nanomaterials in a balloon caninclude, or can be modified to include, a therapeutic agent (e.g., adrug) or a pharmaceutically active compound. As an example, certainceramics are relatively porous. Thus, a therapeutic agent can be loadedonto ceramic nanotubes by, for example, dipping or soaking the ceramicnanotubes in a solution containing the therapeutic agent, and allowingthe therapeutic agent to diffuse through the pores. Suitable ceramicmaterials are described, for example, in U.S. Ser. No. 10/762,816, filedon Jan. 22, 2004, and entitled “Medical Devices”, which is incorporatedherein by reference. As another example, a nanomaterial (e.g.,nanoparticles) can be coated (e.g., spray-coated) with one or moretherapeutic agents. In embodiments in which the balloon includes aprotective layer, the protective layer can also serve as a diffusionlayer that can, for example, regulate the diffusion of therapeutic agentout of the balloon. Therapeutic agents and pharmaceutically activecompounds are described, for example, in Phan et al., U.S. Pat. No.5,674,242; U.S. Patent Application Publication No. US 2003/0185895 A1,published on Oct. 2, 2003; U.S. Patent Application Publication No. US2003/0003220 A1, published on Jan. 2, 2003; and U.S. Patent ApplicationPublication No. US 2003/0018380 A1, published on Jan. 23, 2003. Examplesof therapeutic agents and pharmaceutically active compounds includeanti-thrombogenic agents, thrombogenic agents, antioxidants,anti-inflammatory agents, anesthetic agents, anti-coagulants,anti-restenosis agents, thrombosis agents, immunosuppressant agents, andantibiotics. In some embodiments, a balloon can include more than onetype of therapeutic agent and/or pharmaceutically active compound. Forexample, the balloon can include a first nanomaterial including one typeof therapeutic agent, and a second nanomaterial including another typeof therapeutic agent.

While a rapid-exchange catheter has been described, in certainembodiments, a catheter that includes one of the above-describedballoons can be a different type of rapid-exchange catheter, or can be asingle-operator exchange catheter or an over-the-wire catheter.Single-operator exchange catheters are described, for example, in Keith,U.S. Pat. No. 5,156,594, and in Stivland et al., U.S. Pat. No.6,712,807, both of which are incorporated herein by reference.Over-the-wire catheters are described, for example, in commonly assignedU.S. Patent Application Publication No. US 2004/0131808 A1, published onJul. 8, 2004, which is incorporated herein by reference. In someembodiments, a catheter that includes one of the above-describedballoons can be a fixed-wire catheter. Fixed-wire catheters aredescribed, for example, in Segar, U.S. Pat. No. 5,593,419, which isincorporated herein by reference.

While not shown, in certain embodiments, a balloon that includes one ormore ablated regions that are filled or partially filled with ananomaterial can be an over-the-wire balloon or a fixed-wire balloon,and/or can include one or more cutting elements. Over-the-wire balloonsare described, for example, in Solar, U.S. Pat. No. 4,976,590, which isincorporated herein by reference. Fixed-wire balloons are described, forexample, in Segar, U.S. Pat. No. 5,593,419, incorporated supra. Balloonswith cutting elements are described, for example, in U.S. PatentApplication Publication No. US 2003/0163148 A1, published on Aug. 28,2003; U.S. Patent Application No. US 2004/0133233 A1, published on Jul.8, 2004; and U.S. Ser. No. 10/744,507, filed on Dec. 22, 2003, andentitled “Medical Device Systems”, all of which are incorporated hereinby reference.

In some embodiments, a balloon parison or balloon precursor can becoated with nanomaterial prior to being formed into a balloon.Thereafter, the balloon parison or balloon precursor can be formed intoa balloon.

All publications, applications, references, and patents referred toabove are incorporated by reference in their entirety.

Other embodiments are within the scope of the following claims.

What we claim is:
 1. A balloon catheter, comprising: an elongate shafthaving a proximal end and a distal end; an inflatable balloon positionedadjacent to the distal end of the elongate shaft; a plurality of groovesformed within an exterior surface of the balloon, at least some of theplurality of grooves intersecting at a plurality of intersection pointsand forming a plurality of non-grooved land areas; and a coatingdisposed within the grooves.
 2. The balloon catheter of claim 1, whereinthe coating comprises a nanomaterial.
 3. The balloon catheter of claim2, wherein the nanomaterial is disposed in a matrix polymer.
 4. Theballoon catheter of claim 2, wherein the nanomaterial is bonded to theballoon.
 5. The balloon catheter of claim 1, further comprising a layerdisposed over the coating and the plurality of non-grooved land areas.6. The balloon catheter of claim 5, wherein the layer comprises apolymer.
 7. The balloon catheter of claim 1, wherein the grooves includesubstantially planar walls extending from a substantially planar floor.8. The balloon catheter of claim 1, wherein the grooves have a v-shapedprofile.
 9. The balloon catheter of claim 1, wherein the grooves have ahemispherical profile.
 10. The balloon catheter of claim 1, wherein theinflatable balloon has a burst pressure of at least about 10 atm.
 11. Aballoon catheter, comprising: a catheter shaft having a proximal end anda distal end; an inflatable balloon having a wall having an interiorsurface and an exterior surface defining a wall thickness therebetween;one or more voids formed in the exterior surface of the balloon andextending towards the interior surface defining one or more land areas;a coating comprising a nanomaterial disposed within the one or morevoids; wherein the one or more voids have a wall thickness less than thewall thickness between the interior surface and the surface of theballoon and the one or more land areas have a thickness approximatelyequal to the wall thickness between the interior surface and theexterior surface of the balloon.
 12. The balloon catheter of claim 11,wherein the one or more voids form a pattern comprising a plurality ofintersecting grooves.
 13. A method of forming a medical device,comprising: forming a plurality of grooves in a wall of a medicalballoon to reduce a wall thickness defined between an interior surfaceand an exterior surface of the wall, the plurality of grooves defining apattern of recesses and non-recessed land areas; and adding ananomaterial into the grooves.
 14. The method of claim 13, wherein theplurality of grooves is formed in the wall of the medical balloon whenthe medical balloon is inflated.
 15. The method of claim 13, whereinforming the plurality of grooves in a wall of a medical ballooncomprises ablating the wall of the medical balloon.
 16. The method ofclaim 13, wherein adding a nanomaterial into the grooves comprisescontacting the grooves with a solution comprising the nanomaterial. 17.The method of claim 13, forming a plurality of grooves in a wall of amedical balloon comprises forming a plurality of grooves in a wall of amedical balloon parison and expanding the medical balloon parison. 18.The method of claim 17, wherein forming a plurality of grooves in a wallof a medical balloon parison comprises ablating the wall of the medicalballoon parison.
 19. The method of claim 13, further comprising coatingthe nanomaterial with a polymer after adding the nanomaterial into thegrooves.
 20. The method of claim 19, wherein the polymer comprises anelastomer.